DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of the species of Krebs von den Lungen protein (KL-6) as the biomarker and Nintedanib as the antifibrotic compound of instant claims 5-7, in the reply filed on 10 June 2026 is acknowledged. Applicant indicates claims 1-2 and 4-15 read upon the elected species.
Claims 3 and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Claims 1-2 and 4-15 are examined upon their merits.
Claim Rejections - 35 USC § 112
Claims 1, 2, and 11-13 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of Claims 1, 2, and 11-13 are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons. The biomarkers listed (Claim 1: Krebs von den Lungen protein (KL-6), Pulmonary Surfactant Protein D (SP-D), Matrilysin (MMP7), CA-125 (also named MUC-16), E-selectin, Stromelysin (MVMP3), CA- 19-9, osteopontin (OPN), connective tissue growth factor (CTGF), Cartilage oligomeric matrix protein (COMP), prostasin, von-Willebrand-Faktor (vWF),soluble Intercellular adhesion molecule 1 (sICAM 1) and C-reactive protein (CRP); and, Claim 2: KL-6, SP-D, MMP7, CA-125, E-selectin, sICAM-1, MMP3, CA19-9, OPN, CTGF, COMP, prostasin and vWF) have no substantial structural similarity and are not functional equivalents within the art.
In order to overcome this rejection, Applicant must set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2 and 4-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claim 8 recites “an agent that selectively binds to a prokineticin receptor and inhibits receptor activity”. Claim 1 recites measuring the concentration, expression level or activity of one or more biomarkers and Applicant has elected Krebs von den Lungen protein (KL-6) (a.k.a MUC1; spec. pg.8) for initial prosecution upon the merits and determining or having determined that the activity of the biomarker is modified compared to a respective reference activity of that respective biomarker. The depending claims do not further limit the activity of Krebs von den Lungen protein and are therefore included in the rejection. The claims encompass a genus of “activities”.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see MPEP 2163(II)(3)(a)( i)(A), reduction to drawings MPEP 2163(II)(3)(a) (i)(B), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus MPEP 2163(II)(3)(a) (i)(C). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
In the instant case, the specification fails to describe any relevant activity that is attributed to KL-6. Thus, the claims are drawn to a genus of activities and the instant specification fails to describe the entire genus encompassed by these claims.
While the art at the time of filing KL-6 was implicated in cell-cell adhesion, it is unclear if this is the only activity encompassed by the instant claims. Since, the specification fails to provide a representative number of species within the recited genus of activities. Thus, the specification fails to provide adequate description for the genus encompassed by the claims. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, or representative number of species within the genus of “activities”, the specification does not provide adequate written description of the claimed genus.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Claims 1-2 and 4-15 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for detecting a specific increase in serum concentrations of KL-6 that indicates PF-ILD and treating the disease comprising administering a PDE-4 inhibitor having the structure of Formula A’ (CA index name Cyclobutanemethanol, (5R) (5-chloro-2-pyrimidinyl) -piperidinyl] dihydro-5-oxidothieno[3,2-d]pyrimidin-4-yllamino]; Registry No. 1423719-30-5; common name Nerandomilast a.k.a. BI 1015550) does not reasonably provide enablement for the method comprising measuring any expression level or activity of any of the other listed markers, nor for detecting any other modification other than increased concentration, particularly in serum. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims: With respect to claim breadth, the standard under 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. In addition, when analyzing the scope of enablement, the claims are analyzed with respect to the teachings of the specification and are to be “given their broadest reasonable interpretation consistent with the specification.” See MPEP 2111 [R-5]; Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005); and In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).
As such, the broadest reasonable interpretation of the claimed method is that it provides for an indication of progressive fibrosing interstitial lung disease upon detection of any modification (both increases and decreases) of any concentration, expression or activity of any of the listed biomarkers. For example, this reads upon diagnosing ILD when there is an increase in serum concentrations of KL-6 and also diagnosing the disease when there is a decrease in the relative serum levels of KL-6. A skilled artisan would not know how to use the method with a reasonable expectation of success based solely on what is disclosed in the specification.
The specification teaches that it was already well-established in the art prior to the effective filing date that KL-6 blood concentrations were higher in ILD patients. Page 8 of the specification states: “Regarding fibrosis-related biomarkers it is known from Zhang et al, Curr Opin Pulm Med 212; 18 (5): 441-446 that high blood concentrations of KL-6 (also known as MUC1) have been shown to be predictive of decreased survival in IPF and that high blood plasma concentrations of MMP-7, sICAM-1 and IL-8 were predictive of poor overall survival in IPF-patients. In Stainer et al, Int J Mol Sci 2021, 22, 6255 it is described that different variants of surfactant proteins in serum, such as SP-A and SP-D had been identified as diagnostic markers in IPF: for instance serum levels of SP-D in IPF-patients and in other non-IPF-ILDs had been higher than those in healthy controls and further KL-6 was increased in blood serum of patients suffering from several ILDs including IPF.” Figures 30-32 of the specification, however, demonstrates that KL-6 and MMP7 are decreased during treatment with the PDE4 inhibitor of Nerandomilast. Figure 31 teaches KL-6, SP-D, CA-125 and sICAM-1 seem to have a prognostic potential in IPF patients. Figure 32 states that KL-6, SP-D, E-selectin and sICAM-1 have outcome-related potential during treatment with Nerandomilast. Therefore, what is enabled by the working examples is narrow in comparison to the breadth of the claims.
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentech, Inc, v. Novo Nordisk, 42 USPQ 2d 1001, (CAFC 1997), the court held that:
"[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" and that "[t]ossing out the mere germ of an idea does not constitute enabling disclosure". The court further stated that "when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art", "[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement".
The instant specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, and practice the claimed method without first making a substantial inventive contribution. Given that the nature of the invention is drawn to diagnosis and in vivo treatment, a person having ordinary skill in the art would have to perform multiple further experiments, in order to validate the prognostic potential of all of the listed biomarkers. Specifically, a skilled artisan would have to validate the prognostic potential of Stromelysin (MVMP3), CA- 19-9, osteopontin (OPN), connective tissue growth factor (CTGF), Cartilage oligomeric matrix protein (COMP), prostasin, von-Willebrand-Faktor (vWF), and C-reactive protein (CRP), all of which are listed in the claims, but for which there is no accompanying data. A skilled artisan would also have to determine the directionality of the changes that correlate with disease prognosis. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine’ within the art, and constitutes undue further experimentation in order to use the method with a reasonable expectation of success. Therefore, Claims 1-2 and 4-15 are rejected under 35 U.S.C. 112, first paragraph, for failing to meet the enablement requirement.
The claims were evaluated under 35 USC 101. While the claims recite the mental processes of “comparing” and “determining”, as well as hinging upon the natural phenomenon whereby concentrations of serum KL-6 are associated with PF-ILD, the PDE4 inhibitor having the formula A1, a.k.a. Nerandomilast, was novel in the art of ILD treatment. Therefore, the claim recites a particular treatment that integrates the judicial exception(s) into a practical application thereof.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M..
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/STACEY N MACFARLANE/Examiner, Art Unit 1675
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